Pharmacokinetics and tolerability of lefamulin following intravenous and oral dosing
| Autor: | Steven P Gelone, Werner Heilmayer, Claudia Lell, Wolfgang W Wicha, William T. Prince |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Microbiology (medical) Adolescent 030106 microbiology Administration Oral Pharmacology Bioequivalence Placebo Drug Administration Schedule Cohort Studies Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Oral administration Humans Medicine Polycyclic Compounds Pharmacology (medical) 030212 general & internal medicine Dosing Cross-Over Studies business.industry Fasting Middle Aged Crossover study Healthy Volunteers Anti-Bacterial Agents Bioavailability Infectious Diseases Therapeutic Equivalency Tolerability Supplement Papers Area Under Curve Thioglycolates Administration Intravenous Female Diterpenes business Tablets |
| Zdroj: | Journal of Antimicrobial Chemotherapy |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | Objectives To explore the pharmacokinetics (PK) of oral and intravenous (iv) lefamulin after single and multiple doses, and the effect of food on bioavailability. Methods Lefamulin PK was examined in four studies. In Study 1, PK was assessed in patients with acute bacterial skin and skin structure infections who received repeated iv lefamulin q12h (150 mg). In Study 2, a four-period crossover study, healthy subjects received a single dose of oral lefamulin [immediate-release (IR) tablet, 1 × 600 mg] in a fasted and fed state, oral lefamulin (capsule, 3 × 200 mg) in a fasted state, and iv lefamulin in a fasted state. In Study 3, a three-period crossover study, healthy males received a single oral lefamulin dose (IR) in the following states: fasted, fasted followed by a high-calorie meal 1 h post-dose, and fed. Study 4 had two parts; in part A, healthy males received a single lefamulin dose (IR) in a fasted and fed state; in part B, subjects received repeated doses of lefamulin (IR, q12h) or placebo. Adverse events (AEs) were recorded in each study. Results Single and repeated dosing of iv and oral lefamulin resulted in comparable exposure. Intravenous and oral lefamulin (given fasted or with a meal 1 h post-dose) resulted in bioequivalence. Bioequivalence was not established between oral lefamulin in the fed state and iv or oral administration in the fasted state. All AEs were mild or moderate in severity, no serious AEs were reported, and no participant discontinued because of an AE. Conclusions The PK of lefamulin supports successful switch from iv to oral therapy; lefamulin was generally well tolerated. |
| Databáze: | OpenAIRE |
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